Abstract Background Zhuyeqing Liquor (ZYQL) is a famous traditional Chinese functional liquor. For quality control of ZYQL products, quantitative analysis using high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA) was undertaken. Methods Eighteen compounds from ZYQL were simultaneously detected and used as chemical markers in the quantitative analysis, including 3-hydroxy-4,5(R)-dimethyl-2(5H)-furanone (M1), isobiflorin (M2), vanillic acid (M3), biflorin (M4), genipin 1-O-β-d-gentiobioside (M5), 1-sinapoyl-β-d-glucopyranoside (M6), geniposide (M7), epijasmnoside A (M8), ferulic acid (M9), luteolin 8-C-β-glucopyranoside (M10), isoorientin (M11), narirutin (M12), hesperidin (M13), 6′-O-sinapoylgeniposide (M14), 3,5-dihydroxy-3′,4′,7,8-tetramethoxyl flavones (M15), 3′,4′,3,5,6,8-hexamethoxyl flavone (M16), kaempferide (M17), and tangeretin (M18). Results The separation by gradient elution was achieved on SHIMADZU VP-ODS column (4.6 × 150 mm, 5 μm) at 30°C with methanol (A)/0.1% phosphoric acid (B) as the mobile phase. The detection wavelengths were 254, 278, and 335 nm. The optimized HPLC method provided a good linear relation (r ≥ 0.9991 for all the target compounds), satisfactory precision (RSD values less than 1.47%) and good recovery (97.40% to 103.44%). The limits of detection ranged between 0.20 × 10−4 and 64.90 × 10−4 μg/μL for the different analytes. Furthermore, the optimum sample preparation was obtained from HPD100 column eluted with water and 95% ethanol, respectively. Conclusions Quality control of ZYQL products, in total seven samples and twelve parent plants, was examined by this method, and results confirmed its feasibility and reliability in practice.